Leishmania is not prone to develop resistance to tamoxifen

Autor(es)

Coelho, Adriano C. ^[1] ; Trinconi, Cristiana T. ^[1] ; Senra, Luisa ^[1] ; Yokoyama-Yasunaka, Jenicer K. U. ^[1] ; Uliana, Silvia R. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE; v. 5, n. 3, p. 77-83, DEC 2015.
• Citações Web of Science: 9

Resumo

Tamoxifen, an antineoplastic agent, is active in vitro and in vivo against the parasitic protozoa Leishmania. As part of our efforts to unravel this drug's mechanisms of action against the parasite and understand how resistance could arise, we tried to select tamoxifen-resistant Leishmania amazonensis. Three different strategies to generate tamoxifen resistant mutants were used: stepwise increase in drug concentration applied to promastigote cultures, chemical mutagenesis followed by drug selection and treatment of infected mice followed by selection of amastigotes. For amastigote selection, we employed a method with direct plating of parasites recovered from lesions into semi-solid media. Tamoxifen resistant parasites were not rescued by any of these methods. Miltefosine was used as a control in selection experiments and both stepwise selection and chemical mutagenesis allowed successful isolation of miltefosine resistant mutants. These findings are consistent with a multi-target mode of action to explain tamoxifen's leishmanicidal properties. Considering that drug resistance is a major concern in antiparasitic chemotherapy, these findings support the proposition of using tamoxifen as a partner in drug combination schemes for the treatment of leishmaniasis. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. (AU)

• Processo FAPESP: 11/20484-7 - Tamoxifeno no tratamento de leishmaniose: avaliação de eficácia em esquemas de combinação de drogas e estudo do mecanismo de ação
• Beneficiário: Silvia Reni Bortolin Uliana
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/14629-5 - Mecanismos de ação e resistência à Miltefosina Leishmania spp.
• Beneficiário: Adriano Cappellazzo Coelho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/18858-6 - Tamoxifeno como droga anti-leishmania: atividade em esquemas terapêuticos combinados e estudo do mecanismo de ação
• Beneficiário: Cristiana de Melo Trinconi Tronco
• Modalidade de apoio: Bolsas no Brasil - Doutorado